Chapter 89

Lung cancer is largely a disease of modern man and was considered quite rare before 1900, with fewer than 400 cases described in the medical literature. However, by the mid-twentieth century lung cancer had become epidemic and firmly established as the leading cause of cancer-related death in North America and Europe, killing more than three times as many men as prostate cancer and nearly twice as many women as breast cancer. This fact is particularly distressing since lung cancer is one of the most preventable of all of the common malignancies. Tobacco consumption is the primary cause of lung cancer, a fact firmly established in the mid-twentieth century and codified with the release of the U.S. Surgeon General's 1964 report on the health effects of tobacco smoking. Following the report, cigarette use started to decline in North America and parts of Europe, and with it so did the incidence of lung cancer. To date, the decline in lung cancer is seen most clearly in men; only recently has the decline become apparent among women in the United States. Unfortunately, in many parts of the world, especially in countries with developing economies, cigarette use continues to increase, and along with it, the incidence of lung cancers is also rising. While tobacco smoking remains the primary cause of lung cancer worldwide, more than 60% of new lung cancers occur in never smokers (smoked <100 cigarettes per lifetime) or former smokers (smoked ≥100 cigarettes per lifetime, quit ≥1 year), many of whom quit decades ago. Moreover, 1 in 5 women and 1 in 12 men diagnosed with lung cancer have never smoked. Given the magnitude of the problem, it is incumbent that every internist has a broad knowledge of lung cancer and its management.

Lung cancer is the most common cause of cancer death among American men and women. More than 220,000 individuals will be diagnosed with lung cancer in the United States in 2010. The incidence of lung cancer peaked among men in the late 1980s and has plateaued in women. Lung cancer is rare below age 40, with rates increasing until age 80, after which the rate tapers off. The projected lifetime probability of developing lung cancer is estimated to be approximately 8% among males and approximately 6% among females. The incidence of lung cancer varies by racial and ethnic group, with the highest age-adjusted incidence rates among African Americans. The excess in age-adjusted rates among African Americans occurs only among men, but age-specific rates show that below age 50 mortality from lung cancer is more than 25% higher among African American than Caucasian women. Incidence and mortality rates among Hispanic and Native and Asian Americans are approximately 40–50% those of whites.

### Risk Factors

While the large majority (80–90%) of lung cancers is caused by cigarette smoking, several other factors have been implicated, although none to the extent of tobacco. Cigarette smokers have a tenfold or greater increase in risk of this cancer compared to those who have never smoked. A deep sequencing study suggested that one genetic mutation is induced for every 15 cigarettes smoked. The risk of lung cancer is lower among persons who quit smoking than among those who continue smoking; former smokers have a ninefold increased risk of developing lung cancer compared to ...

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